Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Balversa as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC), harbouring susceptible FGFR3 genetic alterations who have previously received at least one line of therapy containing a PD-1 or PD-L1 inhibitor in the unresectable or metastatic treatment setting (see section 5.1).
Treatment with Balversa should be initiated and supervised by a physician experienced in the use of anticancer therapies.
Before taking Balversa, the physician must have confirmation of (a) susceptible FGFR3 gene alteration(s) (see section 5.1) assessed by a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose. If a CE-marked IVD is not available, an alternative validated test should be used.
The recommended starting dose of Balversa is 8 mg orally once daily. This dose should be maintained and serum phosphate level should be assessed between 14 and 21 days after initiating treatment. Up-titrate the dose to 9 mg once daily if the serum phosphate level is <9.0 mg/dL (<2.91 mmol/L), and there is no drug-related toxicity. If the phosphate level is 9.0 mg/dL or higher follow the relevant dose modifications in Table 2. After day 21 the serum phopshate level should not be used to guide up-titration decision.
If vomiting occurs any time after taking Balversa, the next dose should be taken the next day.
Treatment should continue until disease progression or unacceptable toxicity occurs.
If a dose of Balversa is missed, it can be taken as soon as possible. The regular daily dose schedule for Balversa should be resumed the next day. Extra tablets should not be taken to make up for the missed dose.
For recommended dose reduction schedule, see Tables 1 to 5.
Table 1. Balversa dose reduction schedule:
| Dose | 1st dose reduction | 2nd dose reduction | 3rd dose reduction | 4th dose reduction | 5th dose reduction |
|---|---|---|---|---|---|
| 9 mg (e.g., three 3 mg tablets) | 8 mg (e.g., two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
| 8 mg (e.g., two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
Hyperphosphataemia is an expected, transient pharmacodynamic effect of FGFR inhibitors (see sections 4.4, 4.8 and 5.1). Phosphate concentrations should be assessed prior to the first dose and then monitored monthly. For elevated phosphate concentrations in patients treated with Balversa dose modification guidelines in Table 2 should be followed. For persistently elevated phosphate concentrations, adding a non-calcium containing phosphate binder (e.g., sevelamer carbonate) should be considered as needed (see Table 2).
Table 2. Recommended dose modifications based on serum phosphate concentrations with the use of Balversa after up-titration:
| Serum phosphate concentration | Balversa management |
|---|---|
| For phosphate concentrations >5.5 mg/dL, restrict phosphate intake to 600-800 mg/day. | |
| <6.99 mg/dL (<2.24 mmol/L) | Continue Balversa at current dose. |
| 7.00-8.99 mg/dL (2.25-2.90 mmol/L) | Continue Balversa treatment. Start phosphate binder with food until phosphate level is <7.00 mg/dL. A dose reduction should be implemented for a sustained serum phosphate level of ≥7.00 mg/dL for a period of 2 months or in the presence of additional adverse events or additional electrolyte disturbances linked to prolonged hyperphosphataemia. |
| 9.00-10.00 mg/dL (>2.91-3.20 mmol/L) | Withhold Balversa treatment until serum phosphate level returns to <7.00 mg/dL (weekly testing recommended). Start phosphate binder with food until serum phosphate level returns to <7.00 mg/dL. Re-start treatment at the same dose level (see Table 1). A dose reduction should be implemented for sustained serum phosphate level of ≥9.00 mg/dL for a period of 1 month or in the presence of additional adverse events or additional electrolyte disturbances linked to prolonged hyperphosphataemia. |
| >10.00 mg/dL (>3.20 mmol/L) | Withhold Balversa treatment until serum phosphate level returns to <7.00 mg/dL (weekly testing recommended). Re-start treatment at the first reduced dose level (see Table 1). If serum phosphate level of ≥10.00 mg/dL is sustained for >2 weeks, Balversa should be discontinued permanently. Medical management of symptoms as clinically appropriate (see section 4.4). |
| Significant alteration from baseline renal function or Grade 3 hypocalcaemia due to hyperphosphataemia. | Balversa should be discontinued permanently. Medical management as clinically appropriate. |
Treatment with Balversa should be discontinued or modified based on erdafitinib-related toxicity as described in Table 3.
Table 3. Guideline for management of eye disorders with use of Balversa:
| Severity grading | Balversa dose management |
|---|---|
| Grade 1 Asymptomatic or mild symptoms; clinical or diagnostic observations only, or abnormal Amsler grid test. | Refer for an ophthalmologic examination (OE). If an OE cannot be performed within 7 days, withhold Balversa until an OE can be performed. If no evidence of eye toxicity on OE, continue Balversa at same dose level. If diagnosis from OE is keratitis or retinal abnormality (e.g., CSRa), withhold Balversa until resolution. If reversible in 4 weeks on OE, resume at next lower dose. Upon restarting Balversa, monitor for recurrence every 1-2 weeks for a month and as clinically appropriate thereafter. Consider dose re- escalation if no recurrence. |
| Grade 2 Moderate; limiting age appropriate instrumental activities of daily living (ADL). | Immediately withhold Balversa and refer for an OE. If there is no evidence of eye toxicity, resume erdafitinib therapy at the next lower dose level upon resolution. If resolved (complete resolution or stabilisation and asymptomatic) within 4 weeks on OE, resume Balversa at the next lower dose level. Upon restarting Balversa, monitor for recurrence every 1 to 2 weeks for a month and as clinically appropriate thereafter. |
| Grade 3 Severe or medically significant but not immediate sight-threatening; limiting self-care ADL. | Immediately withhold Balversa and refer for an OE. If resolved (complete resolution or stabilisation and asymptomatic) within 4 weeks, then Balversa may be resumed at 2 dose levels lower. Upon restarting Balversa, monitor for recurrence every 1 to 2 weeks for a month and as clinically appropriate thereafter. Consider permanent discontinuation of Balversa for recurrence. |
| Grade 4 Sight-threatening consequences; blindness (20/200 or worse). | Permanently discontinue Balversa. Monitor until complete resolution or stabilisation. |
a CSR-central serous retinopathy, see section 4.4.
Nail, skin, and mucosal changes have been observed with Balversa. Treatment with Balversa should be discontinued or modified based on erdafitinib-related toxicity as described in Table 4.
Table 4. Recommended dose modifications for nail, skin and mucosal adverse reactions with use of Balversa:
| Severity of adverse reaction | Balversa |
|---|---|
| Nail disorder | Balversa dose management |
| Grade 1 | Continue Balversa at current dose. |
| Grade 2 | Withhold Balversa with reassessment in 1-2 weeks. If first occurrence and it resolves to ≤Grade 1 or baseline within 2 weeks, restart at same dose. If recurrent event or takes >2 weeks to resolve to ≤Grade 1 or baseline, then restart at next lower dose. |
| Grade 3 | Withhold Balversa, with reassessment in 1-2 weeks. When resolves to ≤Grade 1 or baseline, restart at next lower dose. |
| Grade 4 | Discontinue Balversa. |
| Dry skin and skin toxicity | |
| Grade 1 | Continue Balversa at current dose. |
| Grade 2 | Continue Balversa at current dose. |
| Grade 3 | Withhold Balversa (for up to 28 days), with weekly reassessments of clinical condition. When resolves to ≤Grade 1 or baseline, restart at next lower dose. |
| Grade 4 | Discontinue Balversa. |
| Oral mucositis | |
| Grade 1 | Continue Balversa at current dose. |
| Grade 2 | Withold Balversa if the subject has other concomitant erdafitinib related Grade 2 adverse reactions. Withhold Balversa if the subject was already on symptom management for more than a week. If Balversa is withheld, reassess in 1-2 weeks. If this is the first occurrence of toxicity and resolves to ≤Grade 1 or baseline within 2 weeks, restart at same dose. If recurrent event or takes >2 weeks to resolve to ≤Grade 1 or baseline, then restart at next lower dose. |
| Grade 3 | Withhold Balversa, with reassessments of clinical condition in 1- 2 weeks. When resolves to ≤Grade 1 or baseline, restart at next lower dose. |
| Grade 4 | Discontinue Balversa. |
| Dry mouth | |
| Grade 1 | Continue Balversa at current dose. |
| Grade 2 | Continue Balversa at current dose. |
| Grade 3 | Withhold Balversa (for up to 28 days), with weekly reassessments of clinical condition. When resolved to ≤Grade 1 or baseline, restart at next lower dose. |
Table 5. Recommended dose modifications for other adverse reactions with use of Balversa:
| Other adverse reactionsa | |
|---|---|
| Grade 3 | Withhold Balversa until toxicity resolves to Grade 1 or baseline, then may resume Balversa at the next lower dose. |
| Grade 4 | Permanently discontinue. |
a Dose adjustment graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv5.0).
Based on population pharmacokinetic (PK) analyses, no dose adjustment is required for patients with mild or moderate renal impairment (see section 5.2). There are no data on the use of Balversa in patients with severe renal impairment. Alternative treatment should be considered in patients with severe renal impairment (see section 5.2).
No dose adjustment is required for patients with mild or moderate hepatic impairment (see section 5.2). Limited data are available on the use of Balversa in patients with severe hepatic impairment. Alternative treatment should be considered in patients with severe hepatic impairment (see section 5.2).
No specific dose adjustments are considered necessary for elderly patients (see section 5.2). Limited data are available in patients older than 85 years old.
There is no relevant use of erdafitinib in the paediatric population for the treatment of urothelial carcinoma.
Balversa is for oral use. The tablets should be swallowed whole with or without food at about the same time each day.
Grapefruit or Seville oranges should be avoided while taking Balversa due to strong CYP3A4 inhibition (see section 4.5).
There is no known specific antidote for Balversa overdose. In the event of an overdose, stop Balversa, undertake general supportive measures until clinical toxicity has diminished or resolved.
Bottles: 4 years.
Blisters: 3 years.
This medicinal product does not require any special storage conditions.
Bottle:
HDPE (high-density polyethylene) bottle with a child-resistant PP (polypropylene) closure and induction seal liner. Each carton contains one bottle with 28, 56 or 84 film-coated tablets.
3 mg tablet:
4 mg tablet:
5 mg tablet:
3 mg tablet:
4 mg tablet:
5 mg tablet:
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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